Document Detail


Chromatin insulation by a transcriptional activator.
MedLine Citation:
PMID:  12547916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In eukaryotic genomes, transcriptionally active regions are interspersed with silent chromatin that may repress genes in its vicinity. Chromatin insulators are elements that can shield a locus from repressive effects of flanking chromatin. Few such elements have been characterized in higher eukaryotes, but transcriptional activating elements are an invariant feature of active loci and have been shown to suppress transgene silencing. Hence, we have assessed the ability of a transcriptional activator to cause chromatin insulation, i.e., to relieve position effects at transgene integration sites in cultured cells. The transgene contained a series of binding sites for the metal-inducible transcriptional activator MTF, linked to a GFP reporter. Clones carrying single integrated transgenes were derived without selection for expression, and in most clones the transgene was silent. Induction of MTF resulted in transition of the transgene from the silent to the active state, prolongation of the active state, and a marked narrowing of the range of expression levels at different genomic sites. At one genomic site, prolonged induction of MTF resulted in suppression of transgene silencing that persisted after withdrawal of the induction stimulus. These results are consistent with MTF acting as a chromatin insulator and imply that transcriptional activating elements can insulate active loci against chromatin repression.
Authors:
Nathan B Sutter; David Scalzo; Steven Fiering; Mark Groudine; David I K Martin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-01-23
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  100     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-02-05     Completed Date:  2003-03-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1105-10     Citation Subset:  IM    
Affiliation:
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Cell Separation
Chromatin / metabolism*
DNA-Binding Proteins
Dose-Response Relationship, Drug
Flow Cytometry
Genes, Reporter
Green Fluorescent Proteins
Humans
K562 Cells
Luminescent Proteins / metabolism
Plasmids / metabolism
Protein Structure, Tertiary
Time Factors
Transcription Factors / metabolism
Transcriptional Activation*
Transgenes
Grant Support
ID/Acronym/Agency:
HL478790/HL/NHLBI NIH HHS; HL57620/HL/NHLBI NIH HHS; HL65440/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chromatin; 0/DNA-Binding Proteins; 0/Luminescent Proteins; 0/Transcription Factors; 0/transcription factor MTF-1; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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